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��MUCORMYCOSIS IN HEMATOLOGICAL MALIGNANCY�

Presented by

Dr Md Abdulla Almamun Prodhan

MD Phase B Resident

Department Of Hematology

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Objective

Diagnosis and management of Mucormycosis

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CASE SUMMARY

Salma, a-25-year-old normotensive, nondiabetic, a diagnosed case of APML, Low risk, received induction ATRA+ATO for 26 days started from 20.06.2022 to 17.07.2022

On 27.06.22 she required ICU care for dyspnea. She required HFNC for 01day and Polymixin for 10 days

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  • On 16.07.22 she was admitted in BSMMU with fever, cough and dyspnea with spo2 90% with 4-6L oxygen
  • CT Thorax bilateral cavitary consolidation
  • Sputum gram positive Cocci
  • Developed B/L Pneumonia(B/L cavitating consolidation involving all segment of lung)

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CT Scan of chest:

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  • Sputum for C/S, AFB gene expert, fungal stain-negative,
  • P-ANCA and C-ANCA(negative)
  • Patient was intubated and ventilated for 01 day
  • She received antibiotic and antifungal during her hospital stay (Meropenem, Amikacin, Voroconazole, Aciclovir)

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  • Patient discharged from BSMMU on 29.08.22
  • Patient admitted to TMH on 30.08.22
  • Patient presented with worsening cough and dyspnea and had history of hemoptysis.
  • CT bronchial angiogram 30.0 8.22 - multiple variable sized cavitary nodules with bronchial communication in both lung.

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CT Pulmonary Angiogram

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  • Patient underwent Angioembolisation(01.09.22)
  • Again sputum C/S-Klebsiella and Psedumonas aeruginosa.
  • Sputum fungal C/S-aseptate hyphal elements but no growth.
  • sputum PCR did not detect Mucor.

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  • Automated Fungal C/S-Rhizopus species grown.
  • Calcofluor white stain: aseptate hyphal element seen.

She received inj.Amphotericin-B and tab.Levofloxacin from 03.09.22.She switch on to oral antifungal isuvaconazole on 21.09.22 till 24.09.22. Rcurrence of hemoptysis after switch to oral antifungal on 24.09.22

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CT Angiogram on 24.09.22

new area of consolidation is seen in left upper lobe.

A focal aneurysmal dilatation likely of the pulmonary artery in left parahilar region.

There is decreased in size of previously seen cavities in both the lungs.

Patient restart inj amphotericin B instead of oral antifungal.

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  • Case discussed with interventional radiology and planned for coiling of pseudoaneurysm on 09.10.22 but patient attendant refuse to do so conservative treatment is continued.

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Antimicrobial history:

Drug

Duration

Inj amphotericin 200mg OD

03/09/2022- 15/10/2022- contnue as weekly 3 doses

Inj piperacillin tazobactam

09/09/2022- 20/09/2022

Tab. levofloxacin

09/09/2022- 20/09/2022

Tab. isavuconazole

21/09/2022- 24/ 09/2022

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PICTURE OF PATIENT� (With permission of patient)

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OVERVIEW OF

MUCORMYCOSIS

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INTRODUCTION

  • Mucormycosis is the unifying term used to describe infections caused by fungi belonging to the order Mucorales
  • Rhizopus, mucor and rhizomucor species account for up to 75% of mucormycosis cases encountered in hematologic malignancy patient.

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PATHOPHYSIOLOGY

  • The major route of infection is by inhalation of spores
  • Ingestion or traumatic inoculation are recorded

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Clinical Presentation

  • Five clinical forms of mucormycosis:

i. Rhinocerebral ( 44-49%)�ii. Pulmonary (10-11%)�iii. Cutaneous (10-16%)�iv. GI (2-11%)�v. Disseminated, (6-12%) and�vi. Miscellaneous (Renal etc.)�vii. Chronic Mucormycosis �

  • Rhinocerebral type has the highest frequency mortality

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Clinical features of Various Types

i. Rhinocerebral Mucormycosis �Initial symptoms are Nonspecific: Sinusitis, Facial pain, headache, hyposmia etc.

Unilateral Orbital involvement:��Periorbital oedema, ptosis, proptosis, chemosis��Facial numbness

�

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ii. Pulmonary mucormycosis: May occur in isolation or concomitantly with sinusitis

    • Fever
    • Cough
    • Chest pain
    • Shortness of breath
    • Haemoptysis
    • Features of cavitation �

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iii. Cutaneous mucormycosis can look like blisters or ulcers, other symptoms include pain, warmth, excessive redness, or swelling around a wound �iv. Gastrointestinal mucormycosis include

    • Abdominal pain
    • Nausea and vomiting
    • Gastrointestinal bleeding �

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v. Disseminated mucormycosis

  • typically occurs in people who are already sick from other medical conditions
  • Patients with disseminated infection in the brain can�develop mental status changes or coma �

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��Diagnosis �

When to suspect mucormycosis�1. Sinusitis �2. Unilateral facial swelling�3. Blackish discoloration over bridge of nose/palate�4. Chest pain, pleural effusion, haemoptysis, worsening of respiratory symptoms despite conventional therapy. �

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LABORATORY DIAGNOSIS

Systemic fungal infections are detected by β glucan, Galactomannan�But in case of mucormycosis they are not found in serum�

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LABORATORY DIAGNOSIS

Biopsy with histopathologic examination

most sensitive and specific modality for diagnosis.

Culture :�Culture is positive in less than 40% cases .�

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Biopsy Findings:

Wide (6-30µm), thick walled, ribbon like,aseptate hyphal elements that branch at right angles. �

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BIOPSY SPECIMEN

  • Biopsy specimen

Taken from areas of suspected infection such as Necrotic tissue, Tissue from affected Sinuses, Sputum or Bronchoalveolar lavage etc.

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  • Swabs of tissue or discharge

Unreliable for diagnosing this infection�

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RADIOLOGY

​

  • CT scan or MRI of Orbit

in Rhinocerebral Mucormycosis

  • High Resolution CT of Chest

in Pulmonary Mucormycosis

  • MRA/MRV or CTA/CTV-

Cavernous sinus thrombosis or ICA thrombosis �

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MANAGEMENT

To be managed by 3 key strategies:

(1) rapid initiation of effective antifungal therapy.

(2)early surgical debridement of necrotic lesions.

(3) rapid control of underlying medical condition.

�

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�ANTIFUNGAL THERAPY

�Initiation of systemic antifungal therapy: Liposomal Amphotericin B (LAmB)

  • Dose & Duration of LAmB: 5mg/kg Daily,
  • �May be given every alternate day
  • �Patient should be assessed weekly and dose may be escalated upto 10mg/kg
  • Total duration is dependent on the clinical situation.���

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3. Baseline and further follow up investigations:

    • CBC to assess neutropenia
    • Blood sugar
    • S. creatinine
    • S. electrolyte
    • ABG
    • Blood culture –Usually negative
    • CSF study ( in case of CNS Mucormycosis/Meningitis): shows Lymphocytic pleocytosis and elevated Protein �

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Other drugs : Posaconazole, Isavuconazole

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Posaconazole oral solution- 4x200mg twice daily or 2x400 mg per day��

Isavuconaole IV- 3x200 mg day 1-2 followed by 1x200 mg day 3 onwards �

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��How long of treatment is long enough?��

  • Until resolution of signs and symptoms of infection.
  • Resolution of radiographic signs of active disease on serial imaging. �

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Prognosis

Depends on

    • site of infection
    • underlying host factors- hematologic disease and immunosuppression.
    • overall all-cause mortality rate is 54%�

�

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�Prevention, prophylaxis, and infection control �

  • Posaconazole covers Mucorales in high-risk patients when administered as prophylaxis.
  • Meticulous attention to infection control practices.

��

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Take home message

  • Mortality rate is very high
  • So do not miss warning sign symptom
  • Don’t hesitate seeking aggressive investigation to detect fungus.
  • Don’t lose crutial time to initiate treatment.

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THANK YOU